Angelica sinensis polysaccharides ameliorated 5-Fluorouracil-induced damage of early B cell progenitors by alleviating oxidative stress of IL-7 producing mesenchymal stem and progenitor cells

作者全名："Xiao, Hanxianzhi; Wang, Yaping; Wang, Ziling; Wang, Biyao; Hu, Ling; Hou, Jiying; Du, Kunhang; Sun, Nianci; Wang, Lu"

作者地址："[Xiao, Hanxianzhi; Wang, Yaping; Wang, Ziling; Wang, Biyao; Hu, Ling; Hou, Jiying; Du, Kunhang; Sun, Nianci; Wang, Lu] Chongqing Med Univ, Dept Hist & Embryol, Lab Stem Cells & Tissue Engn, Chongqing 400016, Peoples R China; [Xiao, Hanxianzhi] Chongqing Blood Ctr, Chongqing 400015, Peoples R China; [Wang, Lu] Chongqing Med Univ, Dept Hist & Embryol, Lab Stem Cells & Tissue Engn, Chongqing, Peoples R China"

通信作者："Wang, L (通讯作者)，Chongqing Med Univ, Dept Hist & Embryol, Lab Stem Cells & Tissue Engn, Chongqing, Peoples R China."

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001095885300001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：167

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：B cell; Mesenchymal stem and progenitor cell; Osteogenesis; IL-7

摘要："B-lymphocytopenia among myelosuppression is the most intractable side effect of chemotherapy. Here, we investigated ways to alleviate 5-fluorouracil-caused stress hematopoietic impairment. We found that intraperitoneally injected ASP (Angelica sinensis polysaccharides) (100 mg/kg per day), one main active ingredient of Angelica sinensis, for consecutive 7 days, significantly recovered mouse bone marrow pro-B and pre-B cells, reversed the capacity of CFU-PreB colony forming, thus alleviating B cell reduction in the spleen and peripheral blood, as well as ameliorating immunoglobin from spleen and serum. The mechanism is related to the protective effects of ASP on IL-7 producing cells, including perivascular Leptin+ and CXCL12+ mesenchymal stem and progenitor cells (MSPCs), thus promoting IL-7 production, and activating IL-7R-mediated STAT5, PI3K-AKT signaling, including survival signals and EBF1, PAX5 transcription factor expression. Additionally, ASP's IL-7 promoting effect was demonstrated to be associated with maintaining osteogenesis/adipogenesis balance of MSPCs via the NRF2 antioxidant pathway. Collectively, our findings indicate that ASP reverse stress B-lym-phocytopenia via improving Nrf2 signaling, promoting IL-7 production in MSPCs, and subsequently maintaining survival, proliferation, and differentiation of B cell progenitors, which may represent a promising therapeutic strategy."

基金机构：National Natural Science Foundation of China [81873103]; Natural Science Foundation of Chongqing [cstc2021jcyj-msxmX0669]

基金资助正文："<BOLD>Funding</BOLD> This work was supported by the National Natural Science Foundation of China (Grant nos. 81873103) and Natural Science Foundation of Chongqing (Grant nos. cstc2021jcyj-msxmX0669) . The funding body played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript."